These studies are undertaken to study the pathogenesis of the abnormal renal excretion of water in a variety of pathological states. The renal concentrating defect in hypokalemic and hypercalcemic animals is being investigated with attention to both central (vasopressin release-thirst) and renal (cyclic AMP generation, medullary gradient) mechanisms. The role of cellular calcium uptake on renal hemodynamics and sodium excretion is under investigation by employing calcium uptake blockers such as verapamil and proadifen (SKF 525A). Likewise, the importance of cellular calcium on vasopressin release in response to osmotic and nonosmotic stiumli will be assessed. The role of renal hemodynamics and persistent vasopressin secretion in the pathogenesis of the water excretion in edematous disorders such as cirrhosis is being examined. Also, a low output congestive cardiac failure model (pericardial tamponade) will be used to delineate the mechanism of abnormal renal water excretion in this pathophysiological state. An analysis of the effects of hypercapnic acidosis on renal function has been undertaken with attention to renin secretion, sodium excretion and vasopressin release. Studies on the mechanism whereby environmental temperature effects renal water excretion are being completed. The roles of renal hemodynamics, prostaglandins, and antidiuretic hormone responsiveness will be examined in the abnormal renal water excretion associated with thyroid and adrenal insufficiencies. Finally, the mechanism of the defect in renal concentration ability associated with ischemic renal injury will be examined utilizing techniques for papillary plasma flow, and analysis of the tubular cyclic AMP system.